The retinal pigment epithelial (RPE) cell plays a basic role in maintaining the structural and physiological integrity of the neural retina. We have isolated and propagated RPE cells in vitro and have developed monoclonal antibodies directed against human RPE cells. We are using these techniques and reagents to evaluate molecular, biochemical, and biological properties of the RPE cells. Since the monoclonal antibodies detect epitopes present solely on RPE cells, they provide a unique opportunity to evaluate a variety of aspects of RPE cell development and function. Studies on RPE cell development indicate that the epitopes appear only after the cells have begun terminal differentiation. Moreover, studies on RPE migration demonstrate the value of these antibodies in evaluating epiretinal membrane formation. The RPE epitope is a 67 kD protein that is closely associated with the microsomal membrane. A cDNA clone that has been isolated codes for a protein which does not match any other sequences in the data bases. Studies are in progress to propagate and transplant RPE cells in various animals. We have propagated human RPE cells in vitro and evaluated their ability to respond to cytokine activation. RPE cells respond to retinal aberrations by dying, proliferating, migrating, losing phagocytic function, expressing major histocompatibility complex (MHC) class-II antigens, and presenting antigens to T lymphocytes. The techniques and reagents obtained in these studies allow us to evaluate the mechanisms involved in aberrant responses of RPE cells. Moreover, they provide a framework for evaluating RPE cell transplantation.